title: Cold shock Y-box protein-1 proteolysis autoregulates its transcriptional activities.
abstract: BACKGROUND
  The Y-box protein-1 (YB-1) fulfills pleiotropic functions relating to gene transcription, mRNA processing, and translation. It remains elusive how YB-1 shuttling into the nuclear and cytoplasmic compartments is regulated and whether limited proteolysis by the 20S proteasome releases fragments with distinct function(s) and subcellular distribution(s).
  
  
  RESULTS
  To address these questions, mapping of domains responsible for subcellular targeting was performed. Three nuclear localization signals (NLS) were identified. NLS-1 (aa 149-156) and NLS-2 (aa 185-194) correspond to residues with unknown function(s), whereas NLS-3 (aa 276-292) matches with a designated multimerization domain. Nuclear export signal(s) were not identified. Endoproteolytic processing by the 20S proteasome before glycine 220 releases a carboxy-terminal fragment (CTF), which localized to the nucleus, indicating that NLS-3 is operative. Genotoxic stress induced proteolytic cleavage and nuclear translocation of the CTF. Co-expression of the CTF and full-length YB-1 resulted in an abrogated transcriptional activation of the MMP-2 promoter, indicating an autoregulatory inhibitory loop, whereas it fulfilled similar trans-repressive effects on the collagen type I promoter.
  
  
  CONCLUSIONS
  Compartmentalization of YB-1 protein derivatives is controlled by distinct NLS, one of which targets a proteolytic cleavage product to the nucleus. We propose a model for an autoregulatory negative feedback loop that halts unlimited transcriptional activation.
authors.affiliation: Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, Leipziger Str 44, 39120 Magdeburg, Germany. peter.mertens@med.ovgu.de.
authors.forename: Claudia R C
authors.initials: CR
authors.lastname: van Roeyen
authors.forename: Florian G
authors.initials: FG
authors.lastname: Scurt
authors.forename: Sabine
authors.initials: S
authors.lastname: Brandt
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Kuhl
authors.forename: Sandra
authors.initials: S
authors.lastname: Martinkus
authors.forename: Sonja
authors.initials: S
authors.lastname: Djudjaj
authors.forename: Ute
authors.initials: U
authors.lastname: Raffetseder
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Royer
authors.forename: Ioannis
authors.initials: I
authors.lastname: Stefanidis
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Dunn
authors.forename: Steven
authors.initials: S
authors.lastname: Dooley
authors.forename: Honglei
authors.initials: H
authors.lastname: Weng
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Lindquist
authors.forename: Peter R
authors.initials: PR
authors.lastname: Mertens
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D050527:Mesangial Cells / Q000378:metabolism; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals / Q000378:metabolism; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D051381:Rats; D014158:Transcription, Genetic; D051840:Y-Box-Binding Protein 1 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D051840:Y-Box-Binding Protein 1